Four interrelated projects will focus on two major forms and etiologic agents of New World leishmaniasis. The first three of these will address major constraints to control while the latter will investigate more basic questions. Project I will assess vectorial capacity in laboratory-based experimental protocols, and evaluate insecticide susceptibility and targeting to sandfly vectors in laboratory and field studies. In addition, basic questions of sympatric transmission and vector-parasite interactions will be explored within the context of this project. In project II new technological options will be applied to the diagnosis of tegumentary and visceral leishmaniasis. Evaluation criteria will be based on the requirements for control strategies: sensitivity, specificity, positive and negative predictive values, pre-test and post-test likelihood, cost and time considerations. Project III will investigate the mechanisms and molecular mediators of pathogenesis, including atopy, and susceptibility and resistance to L. braziliensis in patients with clinical phenotypes at the extremes of the infection spectrum. Parallel studies of pathogenesis of L. braziliensis infection in the hamster will examine the role of hypersensitivity reactions and modulators of these reactions on the development of metastases, and the question of latent persistence of Leishmania after healing of lesions. In Project IV parasite virulence will be studied. The stability of L. braziliensis karyotype and schizodeme and the possibility of sexual recombination in experimental vertebrate and invertebrate hosts, and the nature and potential role of extrachromosomal DNA and strain-distinguishing gene products in virulence will examined.